P1236: EFFICACY AND TOXICITY FOR CD7 CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY IN PATIENTS WITH RELAPSED/REFRACTORY T-CELL LYMPHOMA
Authors: K. Hu, F. Yang, H. Shi, R. Liu, P. Zheng, S. Feng, Y. Guo
Journal: HemaSphere (2022)

Background: The prognosis of refractory/relapsed T-cell lymphoma is extremely poor, especially for the patients who failed to allogeneic hematopoietic stem cell transplantation(allo-HSCT). Aims: For r/r T-cell lymphoma, a clinical trial using CD7 chimeric antigen receptor T-cell(CD7 CAR-T) has been registered, and the safety and efficacy will be evaluated. Methods: From August 2017 to January 2022, 10 patients were enrolled. The median age was 32(19-72) years old. The diagnosis included T cell lymphoblastic lymphoma(T-LBL,n=8),hepatosplenic T-cell lymphoma(HSTL,n=1)and monomorphic epitheliotropic intestinal T-cell lymphoma(MEITL,n=1). The disease status was progressive disease (PD)in all patients who failed to multi-line therapies, including allo-HSCT (7/10,70%), local irradiation (2/10,20%).Three patients(3/10, 30%)had central nervous system involvement.In order to further reduce the tumor burden, all patients were treated with bridging therapy before CAR-T cell infusion. Before the trial, the expression of CD7 antigen in tumor tissue was positive confirmed by pathology. Patients received FC regimen (fludarabine and cyclophosphamide) before CAR-T cells infusion. The kinetics and function of CAR-T cells was monitored by quantitative PCR and flow cytometry. The efficacy was evaluated by PET-CT as well as bone marrow puncture every 3 month after CAR-T infusion. Results: The median CAR-T cells infused were 1.06×105/kg (range,0.08-24×105/kg). For CAR T cell expansion,the peak time in vivo was on median 14(range,11-29) days after CAR-T cell infusion.The median peak lever of CAR-T cell was 7.94 (range,1.61-49)×107/L, which was no correlation with the number of CAR-T infused. The incidence of cytokine release syndrome (CRS) was 90%(9/10), of which 20% (2/10)was grade 3, as the incidence of severe immune effector cells associated neurologic toxicity (ICANS) (grade 4)was 10%(1/10). Levels of CAR-T cells were very low after the first 1 months postinfusion which detected persistently in 6/10(60%) patients, and the longest lasting time was 355 days post-CAR-T. Although patients’CD7-positive normal T cells were depleted, CD7-negative T cells expanded in all patients.Cytopenias occurred in all patients.Six patients had grade 3 or higher lymphocytopenia, anemia (n=5), thrombocytopenia (n=4), and neutropenia (n=6).Four patients（4/10,40%）had prolonged cytopenias (1 month).1/10(10%) patient of grade IV acute GVHD (intestine) were seen.Viremia and herpes zoster occurred in 4/10(40%) and 2/10(20%) patients respectively. 1/10(10%) patient developed posttransplant lymphoproliferative disorders(PTLD)associated with EBV infection.Altogether,the overall response (ORR) was100% (10/10). Nine patients achieved complete response(CR) (9/10; 90%), one patient of MEITL achieved partial response (PR)(1/10; 10%).With the median follow-up 4.8months (range,3.2-14months), 8 patients survived(8/10,80%),7 patients remained in complete remission at the cutoff date(7/10,70%),and 1 patient of T-LBL achieved PD and survival with tumor(1/10,10%).Two patients(2/11,20%) with T-LBL died of infection. Summary/Conclusion: Our study showed promising efficacy of CD7 CAR-T cell therapy in r/r T-cell lymphoma. CRS is manageable.We need to pay close attention to the incidence of prolonged cytopenias and infection.Long-term follow-up is needed.